Department of Fisheries Biology, College of Fisheries Shirgaon, Rantagiri, Maharashtra, India.
Innovative Informatica Technologies, Mayurinagar, Miyapur, Hyderabad, 500 049, India.
Int J Biol Macromol. 2017 Aug;101:241-253. doi: 10.1016/j.ijbiomac.2017.03.102. Epub 2017 Mar 20.
We report molecular characterization of the kisspeptin receptor (kiss1r), an essential gatekeeper for reproduction and onset of puberty in vertebrates. The full-length cDNA sequence of kiss1r is 1786bp which consist of 5' UTR (untranslated region) 261bp, 3' UTR of 424bp and open reading frame of 1101 encoding a putative protein of 366 amino acids. Basal tissue expression pattern of kiss1r mRNA revealed that it is mainly expressed in the brain and testis. We also report the structure of the kiss1r, along with plausible activation mechanism of this receptor by kisspeptin using computational modelling and dynamic simulation approach of multiple 100ns of timescale. A present modelling and simulations studies shed light on the molecular level of interaction, suggesting that direct hydrogen bonds between ASN4, SER5, GLY7, ARG9 and PHE10 of kisspeptin and TRP7, ASN8, GLU11, ILE17, ASN19 and TYR183 of kiss1r could be crucial role players in initial binding of receptor and the kisspeptin towards allosteric modulatory effects of kisspeptin on the receptor. To the best our knowledge, this is the first report on computational modelling and molecular dynamic simulations of kiss1r in animals shedding light on its possible mode of activation.
我们报告了 kisspeptin 受体（kiss1r）的分子特征，它是脊椎动物生殖和青春期开始的关键门控因子。kiss1r 的全长 cDNA 序列为 1786bp，包括 5'UTR（非翻译区）261bp、3'UTR 424bp 和开放阅读框 1101bp，编码一个假定的 366 个氨基酸的蛋白质。kiss1r mRNA 的基础组织表达模式表明，它主要在大脑和睾丸中表达。我们还报告了 kiss1r 的结构，以及使用计算建模和动态模拟方法对该受体的 kisspeptin 可能的激活机制进行了 100ns 时间尺度的多次模拟。目前的建模和模拟研究揭示了分子水平的相互作用，表明 kisspeptin 中的 ASN4、SER5、GLY7、ARG9 和 PHE10 与 kiss1r 中的 TRP7、ASN8、GLU11、ILE17、ASN19 和 TYR183 之间的直接氢键可能是受体和 kisspeptin 初始结合以及 kisspeptin 对受体的变构调节作用的关键因素。据我们所知，这是动物中 kiss1r 的计算建模和分子动力学模拟的首次报道，揭示了其可能的激活模式。
